Expanding Paradigms of Recessive Dystrophic Epidermolysis Bullosa-Associated Cancer Development and Treatment

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis with no cure. Patients suffer from a wide range of internal and external complications: mechanically induced blistering, chronic wounds, systemic inflammation, among others. Squamous cell carcinoma (SCC) frequently arises at chronic wound sites, where fibrosis and inflammation drive its progression. RDEB-associated SCC is treatment-resistant and highly metastatic, rendering it the major cause of death for patients with RDEB. In this thesis, I present research that encompasses the spectrum of RDEB advancement, from clinical management of cutaneous wounds to RDEB-associated SCC. The central theme of this work is expanding current paradigms of RDEB-associated SCC development and progression, with the ultimate goal of improving strategies available for clinical care. I begin with a general overview of cancer development, metastasis, and treatment. The three manuscripts constituting the primary chapters include a review of drug, cell, and gene therapies for junctional epidermolysis bullosa; a comprehensive analysis of single-cell RNA sequencing from RDEB skin and non-RDEB SCC tumors; and a research paper describing a potentially targetable biomarker of invasion in RDEB-associated SCC. In the conclusion, I consider future prospects of RDEB-focused research and reflect on the evolution of my scientific philosophy.